Chiral Aldehyde Catalysis for the Catalytic Asymmetric Activation of Glycine Esters

Chiral aldehyde catalysis is uniquely
suitable for the direct asymmetric
α-functionalization of N-unprotected amino acids, because aldehydes
can reversibly form imines. However, there have been few successful
reports of these transformations. In fact, only chiral aldehyde catalyzed
aldol reactions of amino acids and alkylation of 2-amino malonates
have been reported with good chiral induction. Here, we report a novel
type of chiral aldehyde catalyst based on face control of the enolate
intermediates. The resulting chiral aldehyde is the first efficient
nonpyridoxal-dependent catalyst that can promote the direct asymmetric
α-functionalization of N-unprotected glycine esters. Possible
transition states and the proton transfer process were investigated
by density functional theory calculations.